Structure and mechanism of imidazoleglycerol-phosphate dehydratase

Steven E. Glynn; Patrick J. Baker; Svetlana E. Sedelnikova; Claire L. Davies; Thomas C. Eadsforth; Colin W. Levy; H. Fiona Rodgers; G. Michael Blackburn; Timothy R. Hawkes; Russell Viner; David W. Rice

doi:10.1016/j.str.2005.08.012

Structure and mechanism of imidazoleglycerol-phosphate dehydratase

Steven E. Glynn, Patrick J. Baker, Svetlana E. Sedelnikova, Claire L. Davies, Thomas C. Eadsforth, Colin W. Levy, H. Fiona Rodgers, G. Michael Blackburn, Timothy R. Hawkes, Russell Viner, David W. Rice

Mechanical and Aerospace Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

The structure of A. thaliana imidazoleglycerol-phosphate dehydratase, an enzyme of histidine biosynthesis and a target for the triazole phosphonate herbicides, has been determined to 3.0 Å resolution. The structure is composed of 24 identical subunits arranged in 432 symmetry and shows how the formation of a novel dimanganese cluster is crucial to the assembly of the active 24-mer from an inactive trimeric precursor and to the formation of the active site of the enzyme. Molecular modeling suggests that the substrate is bound to the manganese cluster as an imidazolate moiety that subsequently collapses to yield a diazafulvene intermediate. The mode of imidazolate recognition exploits pseudosymmetry at the active site arising from a combination of the assembly of the particle and the pseudosymmetry present in each subunit as a result of gene duplication. This provides an intriguing example of the role of evolution in the design of Nature's catalysts.

Original language	English
Pages (from-to)	1809-1817
Number of pages	9
Journal	Structure
Volume	13
Issue number	12
DOIs	https://doi.org/10.1016/j.str.2005.08.012
Publication status	Published - Dec 2005

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title = "Structure and mechanism of imidazoleglycerol-phosphate dehydratase",

abstract = "The structure of A. thaliana imidazoleglycerol-phosphate dehydratase, an enzyme of histidine biosynthesis and a target for the triazole phosphonate herbicides, has been determined to 3.0 {\AA} resolution. The structure is composed of 24 identical subunits arranged in 432 symmetry and shows how the formation of a novel dimanganese cluster is crucial to the assembly of the active 24-mer from an inactive trimeric precursor and to the formation of the active site of the enzyme. Molecular modeling suggests that the substrate is bound to the manganese cluster as an imidazolate moiety that subsequently collapses to yield a diazafulvene intermediate. The mode of imidazolate recognition exploits pseudosymmetry at the active site arising from a combination of the assembly of the particle and the pseudosymmetry present in each subunit as a result of gene duplication. This provides an intriguing example of the role of evolution in the design of Nature's catalysts.",

author = "Glynn, {Steven E.} and Baker, {Patrick J.} and Sedelnikova, {Svetlana E.} and Davies, {Claire L.} and Eadsforth, {Thomas C.} and Levy, {Colin W.} and Rodgers, {H. Fiona} and Blackburn, {G. Michael} and Hawkes, {Timothy R.} and Russell Viner and Rice, {David W.}",

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doi = "10.1016/j.str.2005.08.012",

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AU - Glynn, Steven E.

AU - Baker, Patrick J.

AU - Sedelnikova, Svetlana E.

AU - Davies, Claire L.

AU - Eadsforth, Thomas C.

AU - Levy, Colin W.

AU - Rodgers, H. Fiona

AU - Blackburn, G. Michael

AU - Hawkes, Timothy R.

AU - Viner, Russell

AU - Rice, David W.

PY - 2005/12

Y1 - 2005/12

N2 - The structure of A. thaliana imidazoleglycerol-phosphate dehydratase, an enzyme of histidine biosynthesis and a target for the triazole phosphonate herbicides, has been determined to 3.0 Å resolution. The structure is composed of 24 identical subunits arranged in 432 symmetry and shows how the formation of a novel dimanganese cluster is crucial to the assembly of the active 24-mer from an inactive trimeric precursor and to the formation of the active site of the enzyme. Molecular modeling suggests that the substrate is bound to the manganese cluster as an imidazolate moiety that subsequently collapses to yield a diazafulvene intermediate. The mode of imidazolate recognition exploits pseudosymmetry at the active site arising from a combination of the assembly of the particle and the pseudosymmetry present in each subunit as a result of gene duplication. This provides an intriguing example of the role of evolution in the design of Nature's catalysts.

AB - The structure of A. thaliana imidazoleglycerol-phosphate dehydratase, an enzyme of histidine biosynthesis and a target for the triazole phosphonate herbicides, has been determined to 3.0 Å resolution. The structure is composed of 24 identical subunits arranged in 432 symmetry and shows how the formation of a novel dimanganese cluster is crucial to the assembly of the active 24-mer from an inactive trimeric precursor and to the formation of the active site of the enzyme. Molecular modeling suggests that the substrate is bound to the manganese cluster as an imidazolate moiety that subsequently collapses to yield a diazafulvene intermediate. The mode of imidazolate recognition exploits pseudosymmetry at the active site arising from a combination of the assembly of the particle and the pseudosymmetry present in each subunit as a result of gene duplication. This provides an intriguing example of the role of evolution in the design of Nature's catalysts.

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SN - 0969-2126

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EP - 1817

JO - Structure

JF - Structure

IS - 12

ER -

Structure and mechanism of imidazoleglycerol-phosphate dehydratase

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